Display options
Cite
Mu L, Zhou R, Tang F, et al. Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites. Acta Pharm Sin B. 2015;6(2):158-62doi: 10.1016/j.apsb.2015.10.002.
Mu, L., Zhou, R., Tang, F., Liu, X., Li, S., Xie, F., Xie, X., Peng, J., & Yu, P. (2016). Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites. Acta pharmaceutica Sinica. B, 6(2), 158-62. https://doi.org/10.1016/j.apsb.2015.10.002
Mu, Lingli, et al. "Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites." Acta pharmaceutica Sinica. B vol. 6,2 (2016): 158-62. doi: https://doi.org/10.1016/j.apsb.2015.10.002
Mu L, Zhou R, Tang F, Liu X, Li S, Xie F, Xie X, Peng J, Yu P. Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites. Acta Pharm Sin B. 2016 Mar;6(2):158-62. doi: 10.1016/j.apsb.2015.10.002. Epub 2015 Dec 21. PMID: 27006900; PMCID: PMC4788712.
Copy Download .nbib Format: NLM
Share it on

Acta Pharm Sin B. 2016 Mar;6(2):158-62. doi: 10.1016/j.apsb.2015.10.002. Epub 2015 Dec 21.

Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites.

Acta pharmaceutica Sinica. B

Lingli Mu, Rui Zhou, Fang Tang, Xingling Liu, Sanwang Li, Feifan Xie, Xiang Xie, Jie Peng, Peng Yu

Affiliations

  1. Medical College, Hunan Normal University, Changsha 410006, China.
  2. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.

PMID: 27006900 PMCID: PMC4788712 DOI: 10.1016/j.apsb.2015.10.002

Abstract

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.

Keywords: Intracellular kinetic; LC–MS/MS; Metabolites; Pharmacokinetics; Phosphates; Zidovudine; hPBMCs

References

  1. Clin Ther. 2000 Jun;22(6):685-708 - PubMed
  2. Gen Pharmacol. 1998 Oct;31(4):531-8 - PubMed
  3. Br J Clin Pharmacol. 1994 May;37(5):401-4 - PubMed
  4. Ann Neurol. 1991 Jun;29(6):606-14 - PubMed
  5. J Biol Chem. 1999 Aug 20;274(34):23814-9 - PubMed
  6. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1911-5 - PubMed
  7. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333-7 - PubMed
  8. J Biol Chem. 1994 Apr 29;269(17):12633-8 - PubMed
  9. J Neurol Sci. 1997 Jul;149(1):19-25 - PubMed
  10. Cardiovasc Toxicol. 2004;4(2):155-67 - PubMed
  11. J Trop Pediatr. 2006 Aug;52(4):244-8 - PubMed
  12. J Infect Dis. 1996 Sep;174(3):490-9 - PubMed
  13. Antivir Ther. 2005;10(5):615-24 - PubMed
  14. J Med Assoc Thai. 2008 Dec;91(12):1925-35 - PubMed
  15. Biochem Pharmacol. 1988 Jul 15;37(14):2847-56 - PubMed
  16. N Engl J Med. 1990 Apr 19;322(16):1098-105 - PubMed

Publication Types